Cryptococcal meningitis (CM) is the second most common AIDS defining illness in Sub-Saharan Africa. Even with the availability of antiretroviral therapy (ART), the survival of ARTna[unreadable]ve patients after CM is poor. In two recent cohorts, the six month survival after cryptococcus was only 30-40% even though ART was available. In a 136 person Ugandan cohort studied by our research group, 40% mortality occurred in the time between CM diagnosis and the expected time of ART initiation, which occurred at a median delay of 5 weeks from diagnosis. In Uganda, as in the rest of the world, the standard practice is to start ART as an outpatient, but this practice leads to considerable delay in restoring immunity in ill patients who are profoundly immunosuppressed. A theoretical, but unproven, risk of earlier ART is increased risk of HIV Immune Reconstitution Inflammatory Syndrome (IRIS). The mortality with CM-related IRIS can be high (30-60%). We plan to conduct the definitive trial to determine the optimal time to start ART after cryptococcal meningitis in HIV-infected Ugandan patients. The primary outcome measure of the trial is survival with secondary outcomes being the incidence of IRIS, virologic success, and cryptococcal microbiologic treatment success. Hypothesis: Early ART initiated within 14 days of cryptococcal diagnosis will result in improved survival through six months versus the current standard of initiating ART as an outpatient 4-6 weeks after CM diagnosis. We hypothesize that earlier ART initiation will reduce the delayed mortality of 20% in the time to starting ART as an outpatient. Specific Aim #1: To plan a phase IV randomized controlled trial to determine the optimal timing of initiating ART after cryptococcal meningitis. Specific Aim #2: To develop all documentation required for initiation of the randomized trial, including a detailed study protocol, data monitoring plan, standard operating procedures, study manuals, and staff training in good clinical practices. Specific Aim #3: To complete all local, federal, and international human subjects and regulatory approvals necessary for implementation of the trial, including the formation of a Data Monitoring Safety Board (DMSB) to review interim analyses.